ObjectiveTo review the research advances in molecular biology of vascular restenosis.MethodsThe literatures about molecular biology of vascular restenosis were reviewed.ResultsCurrent transgenic ways had some advantages and disadvantages. Gene therapy with HSV-tk, Rb,p21，p27,p53,c-myc, c-myb, vascular endothelial growth factor,bFGF,platelet derived growth facfor，nuclear factor-κB and so on inhibited vascular restenosis.ConclusionA better transgenic system and gene-combination therapy will be effective to treat vascular restenosis.
ObjectiveTo systematically evaluate the outcomes of drug-eluting balloon (DEB) in treating coronary artery in-stent restenosis (ISR) by using meta-analysis and trial sequential analysis (TSA). MethodsWe searched PubMed, EMbase, The Cochrane Library（Issue 4, 2016）, CNKI, CBM, VIP and WanFang Data to collect randomized controlled trials (RCTs) regarding the treatment of ISR by DEB from inception to April 2016. After two reviewers independently screened citations, extracted data and assessed the bias risk of included studies, we carried out meta-analysis and TSA analysis by using RevMan 5.3 version and TSA v0.9 respectively. ResultsA total of 10 RCTs involving 1909 patients were included. Seven-hundred and forty-seven patients were included with regard to the comparison between DEB and POBA, 1162 patients were recruited to compare DEB and drug-eluting stents (DES). The results of meta-analysis revealed that DEB was associated with decreased mortality (OR=0.36, 95%CI 0.14 to 0.93, P=0.04), compared with that of plain old balloon angioplasty (POBA). And TSA showed that cumulative Z-curve strode the conventional threshold value but not the TSA threshold value which suggested a false positive result of meta-analysis. In comparison with that of POBA, DEB had a lower incidence of target lesion revascularization (TLR) (OR=0.16, 95%CI 0.07 to 0.38, P＜0.01). And the result of TSA displayed that the cumulative Z-curve strode both the conventional and TSA threshold value which validated the result of meta-analysis. Besides, the results of meta-analysis showed that there were no significant differences in mortality (OR=0.84, 95%CI 0.41 to 1.72, P=0.63) and TLR (OR=1.55, 95%CI 0.76 to 3.16, P=0.22) between DEB and DES. However, the result of TSA revealed that the cumulative Z-curve did not strode both the conventional and TSA threshold value, and the included sample size less was than required information size which suggested that the reliability of the meta-analysis needed more studies to confirm. While the subgroup analysis of EES revealed that DEB had a higher incidence of TLR than that of DEB (OR=3.37, 95%CI 1.59 to 7.15, P＜0.01). And the result of TSA displayed that the cumulative Z-curve strode both the conventional and TSA threshold value which validated the result of meta-analysis. ConclusionCurrent evidence shows, EES is superior to DEB in decreasing the incidence of TLR in patients with ISR, while DEB is superior to POBA. However, the comparison of DEB and other strategies on reducing of mortality in patients with ISR still needed more studies to prove.
ObjectiveTo investigate the effect of simvastatin and mechanical pretreatment on intimal hyperplasia of venous graft and its mechanism.MethodsTwelve New Zealand rabbits were selected and randomly divided into 4 groups: a blank control group, a simvastatin topical treatment group, a mechanical precondition group and a combined group (n=3 in each group). Ultrasound was used to evaluate the changes of graft wall and blood flow velocity in the graft, and pathological section was used to evaluate the intimal hyperplasia. Human umbilical cord endodermal cells were cultured in vitro. A simvastatin group and a solvent control group were set to detect YAP phosphorylation, downstream target gene expression and cell proliferation.ResultsVascular ultrasound showed that except the simvastatin topical treatment group, the flow velocity in vein grafts in the other three groups significantly increased 21 days after surgery compared with 7 days after surgery (P<0.01). Pathological sections showed that the thickness of new intima in the simvastatin topical treatment group, mechanical precondition group, combined group and blank control group were 45.56±4.11 μm, 201.28±16.71 μm, 143.57±7.82 μm, 249.45±13.33 μm, respectively, and there were statistical differences compared with the blank control group (P<0.05). In vitro results showed that compared with the solvent control group, cell death was observed in high concentration simvastatin (5 mmol/L) group, cell proliferation was inhibited in low concentration simvastatin (2.5 mmol/L) group (P<0.05), the expression of YAP protein in the simvastatin group was unchanged, but the expression of phosphorylated YAP protein significantly increased (P<0.05), and the expression of downstream target gene ccn1 was down-regulated (P<0.001).ConclusionIntravascular local application of simvastatin and mechanical preconditioning alone or in combination can inhibit intimal hyperplasia of venous graft. High concentration of simvastatin has cytotoxicity, while low concentration of simvastatin has inhibitory effect on cell proliferation. Simvastatin can inhibit the formation of new intima by inhibiting the entry of YAP into the nucleus and reducing the transcription of cell proliferation-related target gene ccn1.
ObjectiveTo study the prevention and treatment of restenosis after the stent placement in the latest progress. MethodsThere were four methods including drug-eluting stents, intracavitary illuminate, drug therapy, and mesenchymal stem cells, which prevented or treatment restenosis after stent placement. ResultsAll the four methods could reduce the postoperative restenosis rate after interventional treatment. Many experimental study of prevention and treatment of restenosis had obvious effect, but clinical curative effect was not very satisfactory, because of a series of problems such as safety, animal models, experiment method, and so on. ConclusionThe multiple factors and links caused restenosis should be considered fully, and interrupting the links or factors as far as possible could control the occurrence or development effectively.
Objective To determine whether local delivery of c-myc shRNA could inhibit hyperplasia and lithogenic potentiality in a rat model of chronic proliferative cholangitis (CPC) via specific blockade of the c-myc expression. Methods The CPC animal model (CPC group) was established via retrograde insertion of a 5-0 nylon thread into the common bile duct through Vater’s papilla. Three kinds of c-myc shRNAs were then respectively injected in c-myc shRNA group, which were included shRNA-1, shRNA-2, and shRNA-3, respectively. Negative control group and sham operation group were established for comparison. Subsequently, histopathological changes of bile duct wall were observed by HE, Massion, and PAS/AB staining; c-myc protein was detected by immunohistochemistry method; 5-bromodeoxyuridine (BrdU) protein was tested by immumofluorescence method; c-myc, Mucin 3, and Procollagen Ⅰ mRNAs were detected by real time PCR; Ki-67 protein was determined by Western blot; Activity of β-glucuronidase was measured by modified Fisherman method. Results ①Compared with the CPC and negative control groups, biliary tract mucosa epithelium (HE staining), submucosal acid mucinous gland (mid-blue staining, PAS/AB staining), and degree of over-hyperplasia of collagen fiber in bile duct wall (blue staining, Massion staining) were weaker in the c-myc shRNA group. ②The expressions of c-myc mRNA, Mucin 3 mRNA, Procollagen Ⅰ mRNA, Ki-67 protein, and β-G activity in the c-myc shRNA group were lower than those of the CPC and negative control groups (Plt;0.05), but higher than those of the sham operation group (Plt;0.05). Conclusion c-myc shRNA treatment could effectively inhibit the hyperplastic behavior and lithogenic potential of CPC, which might help to prevent the biliary restenosis and stone recurrence.
ObjectiveTo evaluate the safety and mid-to-long term outcomes of catheter-directed thrombolysis (CDT) in combination with percutaneous mechanical thrombectomy (PMT) followed by stent placement treatment for acute proximal deep vein thrombosis (DVT) complicated by iliac vein compression syndrome (IVCS), and to identify risk factors relevent to primary stent restenosis. MethodsA retrospective study was conducted. The patients diagnosed with acute proximal DVT and concurrent IVCS who underwent CDT in combination with PMT followed by stent placement at the First Affiliated Hospital of Chongqing Medical University from January 2018 to December 2021 were included. The demographics, clinical history, and procedural data were collected. The postoperative follow-up using color Doppler ultrasound were scheduled at 3, 6, and 12 months, and annually thereafter. The primary and secondary stent patency rates were evaluated. The univariate and multivariate Cox proportional hazards regression models were employed to assess risk factors for primary stent restenosis. ResultsA total of 188 patients who met the inclusion and exclusion criteria were enrolled, underwent CDT combined with PMT and stent implantation, and completed follow-up. During the follow-up, the restenosis occurred in 26 patients. The cumulative primary patency rates at 3, 6, 12, 24, 36, and 48 months after surgery were 100%, 98.9%, 92.5%, 88.3%, 86.7%, and 86.2%, respectively. The multivariate Cox proportional hazards regression analysis confirmed that a history of previous DVT [HR (95%CI)=4.21 (1.73, 10.28), P=0.002], implantation of two or more stents [HR (95%CI)=11.85 (1.66, 84.63), P=0.014], stent crossing the inguinal ligament [HR (95%CI)=9.92 (1.87, 52.78), P=0.007], and stent length [HR (95%CI)=0.98 (0.97, 0.99), P=0.003] were the affecting factors for primary restenosis. ConclusionsThe findings of this study suggest that CDT combined with PMT and stent implantation is a safe and effective strategy for treating acute proximal DVT complicated by IVCS. Close attention should be paid to the occurrence of restenosis in patients with two or more stents, stent crossing the inguinal ligament, and a history of previous DVT.
Cardiovascular disease is one of the most common causes of death. Coronary artery stent implantation has been the most important method to cure coronary disease and inhibit angiostegnosis. However, restenosis and thrombus at the site of implanting cardiovascular devices remains a significant problem in the practice of interventional cardiology. Recently, lots of studies have revealed that endothelial impairment is considered as one of the most important mechanisms contributing to restenosis. As a result, the method of accelerating endothelial regeneration at the injury site could prevent restenosis and thrombus. Considering the surface modification of cardiovascular stent implantation, this paper summarizes the progress on this direction, especially for the prevention of cardiovascular restenosis. Furthermore, this paper also proposes the methods and the future developing prospects for accelerating in vivo re-endothelialization at the site of intravascular stent with different biological molecules.
Coronary atherosclerotic heart disease is a serious threat to human life and health. In recent years, the main treatment for it is to implant the intravascular stent into the lesion to support blood vessels and reconstruct blood supply. However, a large number of experimental results showed that mechanical injury and anti-proliferative drugs caused great damage after stent implantation, and increased in-stent restenosis and late thrombosis risk. Thus, maintaining the integrity and normal function of the endothelium can significantly reduce the rate of thrombosis and restenosis. Stem cell mobilization, homing, differentiation and proliferation are the main mechanisms of endothelial repair after vascular stent implantation. Vascular factor and mechanical microenvironmental changes in implanted sites have a certain effect on re-endothelialization. In this paper, the process of injury caused by stent implantation, the repair mechanism after injury and its influencing factors are expounded in detail. And repairing strategies are analyzed and summarized. This review provides a reference for overcoming the in-stent restenosis, endothelialization delay and late thrombosis during the interventional treatment, as well as for designing drug-eluting and biodegradation stents.
Objective To investigate the influencing factors for restenosis after femoral endarterectomy in treatment of arteriosclerosis obliterans at femoral artery . Methods A total of 103 patients with arteriosclerosis obliterans at femoral artery who underwent femoral endarterectomy from Jan. 2012 to Jan. 2017 in our hospital were retrospectively selected as subjects of this study, to compare the clinical feathers between restenosis group and patent group, and then exploring the influencing factors for restenosis after femoral endarterectomy. Results Thirty-six patients (35.0%) suffered from restenosis after femoral endarterectomy. Patients in the restenosis group had a high proportion of high smoking and diabetes mellitus, and high level of low density lipoprotein than those corresponding indexes of the patent group (P<0.05). Results of Cox proportional hazard model showed that, diabetes mellitus 〔RR=3.338, 95% CI was (1.003, 11.113), P=0.049〕 and high level of low density lipoprotein 〔RR=3.311, 95% CI was (1.166, 9.397), P=0.024〕 were independent risk factors for restenosis after femoral endarterectomy. Conclusions Monitoring of high-risk factors like controlling blood glucose strictly and strengthening statin treatment should be done to reduce the risk of restenosis after femoral endarterectomy for patients with arteriosclerosis obliterans at femoral artery.
Objective To investigate the expression of neutrophil gelatinase-associated lipocalin (NGAL) signaling pathways in the early stage of porcine vein graft restenosis, and to explore the possible role and mechanism in the early vein graftrestenosis after coronary artery bypass surgery. Methods We selected 18 ordinary healthy pigs weighing 25-30 kg and collected samples of the vein graft of pigs at the preoperation and postoperative days 7, 14 and 30. Hematoxylin-eosin (HE) staining and Masson staining, immunohistochemical method were used to observe the neointimal hyperplasia, the migration of smooth muscle cells and and vascular remodeling of the vein bypass graft. The expression changes of NGAL, matrix metalloprotenase (MMP)9, MMP2 and tissue inhibitor of metalloproteinase (TIMP)1 in different periods of the vein bypass graft was tested. Results By HE and Masson staining, with the passing of modeling time, degradation of collagen matrix in the vein graft, gradually thickening of muscle fibers and the migration to the inner membrance and vascular remodeling caused the vascular stenosis. By immunohistochemistry, NGAL, MMP9 and MMP2 of normal vein in the model were seldom expressed and even did not express. At 14 days after the modeling, NGAL expression in the membrane layer of blood vessels began to appear, peaked at postoperative 30 days, and began to appear in the inner membrance. MMP9, MMP2 expression began to appear at postoperative 7 days, peaked at postoperative 14 days, and tended to decline at postoperative 30 days. TIMP1 expression was less in normal vascular walls and at the 14 days after the modeling, expression peaked in the vein graft. Conclusion NGAL, MMP9, MMP2 and TIMP1 may be involved in the formation of early vascular graft restenosis. NGAL as initiator, results in the expression of MMP9 and MMP2, and participates in the degradation of collagen matrix and the migration of smooth muscle cells in vein grafts. TIMP1 as a negative factor, may play an important role in maintaining their own balance.